The emerging risk of overdiagnosis in rheumatoid arthritis and polymyalgia rheumatica.

Overdiagnosis occurs when patients are diagnosed with a disease that would otherwise never have affected the quality or duration of their lives. This often happens unintentionally through well-meaning screening programmes that aim to detect diseases during so-called subclinical stages. Recently, it has been suggested that patients with polymyalgia rheumatica should be screened for giant cell arteritis to identify those at higher risk of relapse or vascular complications. Screening for interstitial lung disease for patients with rheumatoid arthritis has also been recommended to identify patients who could benefit from pulmonary interventions. These potential benefits must be weighed against foreseeable harms. Such harms include the uncovering of incidental findings that necessitate additional medical follow-up, the financial costs associated with screening initiatives, the risk of overtreatment through increased immunosuppression in patients who might not have otherwise required it, and the psychosocial burden of a new diagnosis. Randomised clinical trials and prospective cohort studies of screening interventions should be conducted to establish the risks and benefits and identify patients most likely to benefit from them. This Viewpoint covers risks that overdiagnosis presents to the field of rheumatology, with focus on rheumatoid arthritis and polymyalgia rheumatica.

Positive and negative controls in rheumatology research.

Observational research from large population databases may be affected by unmeasured confounding and time-related biases, such as immortal time bias. Modern causal inference practice applies propensity score-based methods, new-user designs, and other strategies to mitigate bias. The degree to which these methodologic approaches adequately address bias for any particular study may be difficult to measure. Recently, the incorporation of positive and negative controls has been identified as a means to assess for the impacts of residual confounding and/or time-related biases. The objective of this commentary is to describe the role of positive and negative controls in observational research. We offer recommendations for incorporating controls into critical appraisal and observational research projects.

Risk factors for mortality within 5 years of carotid endarterectomy for asymptomatic stenosis.

OBJECTIVE: The current Society for Vascular Surgery guidelines for the treatment of patients with asymptomatic carotid stenosis recommend endarterectomy for patients with >70% stenosis and acceptable surgical risk. The reduced rate of stroke with modern medical therapy has increased the importance of careful selection in deciding which patients should undergo elective carotid endarterectomy (CEA) for asymptomatic disease. It would, therefore, be very prudent to investigate preexisting variables predictive of 5-year mortality for patients meeting the criteria to undergo CEA. METHODS: The Vascular Quality Initiative was queried from 2003 onward for all cases of CEA. Inclusion in the study required the following: (1) documentation of survival status; (2) complete data on all incorporated demographic study variables; and (3) asymptomatic neurologic status. The variables present at surgery were investigated using binary logistic regression to identify multivariate predictors of 5-year mortality. The highest risk variables were then interrogated for an additive effect regarding long-term mortality. A subanalysis was performed for patients aged >80 years. RESULTS: A total of 30,615 patients met the inclusion criteria, 5414 (18%) of whom had died within 5 years. The highest risk variables were classified as those that had had an adjusted odds ratio >1.25, P < .001, and beta coefficient of ≥0.25. These included a body mass index <20 kg/m2, diabetes mellitus, a history of congestive heart failure, renal insufficiency, end-stage renal disease, chronic obstructive pulmonary disease, living status other than home, prior lower extremity bypass, prior major amputation, Black race relative to other races combined, hemoglobin <10 mg/dL, a history of neck irradiation, and a history of smoking. Age had an annual odds ratio of 1.04 (P < .001). Other variables that achieved a statistically significant (P < .05) association with 5-year mortality were coronary artery disease, a positive stress test or the occurrence of myocardial infarction within 2 years, lower extremity arterial intervention, aneurysm repair, and P2Y12 inhibitor therapy at surgery. The use of statin and aspirin therapy at surgery were both protective against 5-year mortality (P < .001). CONCLUSIONS: We identified 12 particularly high-risk variables, which, in combination, progressively predicted for increasing mortality within 5 years of CEA performed for asymptomatic stenosis. Special attention should be given to patients aged >80 years and patients with any history of congestive heart failure regardless of current symptoms, chronic obstructive pulmonary disease, renal insufficiency or end-stage renal disease, peripheral artery disease, diabetes, and variables associated with frailty (BMI under 20, anemia, assisted living status).

Structural racism is a mediator of disparities in acute myeloid leukemia outcomes.

Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic White (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult patients with AML from 6 urban cancer centers and revealed inferior survival among NHB (hazard ratio [HR] = 1.59; 95% confidence interval [CI]: 1.15, 2.22) and Hispanic (HR = 1.25; 95% CI: 0.88, 1.79) patients compared with NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across 6 composite variables: structural racism (census tract disadvantage, affluence, and segregation), tumor biology (European Leukemia Network risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization), and intensive care unit (ICU) admission during induction chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, and treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.